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Rationale: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis and access to affordable interventions. There are no previous reports describing therapeutic needs of populations with COPD in LMICs who were identified through screening. Objectives: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. Methods: We compared interventions recommended by the international Global Initiative for Chronic Obstructive Lung Disease COPD strategy document, with that received in 1,000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru, and Uganda. We calculated costs using data on the availability and affordability of medicines. Measurement and Main Results: The greatest unmet need for nonpharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%), and advice on biomass smoke exposure (26%). Ninety-five percent of the cases were previously undiagnosed, and few were receiving therapy (4.5% had shortacting β-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable, with 30 days of treatment costing more than a low-skilled worker's daily average wage. Conclusions: We found a significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Although there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis combined with access to affordable interventions could translate to immediate benefit. [ABSTRACT FROM AUTHOR]

Importance: Most of the global morbidity and mortality in chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs), with significant economic effects.Objective: To assess the discriminative accuracy of 3 instruments using questionnaires and peak expiratory flow (PEF) to screen for COPD in 3 LMIC settings.Design, Setting, and Participants: A cross-sectional analysis of discriminative accuracy, conducted between January 2018 and March 2020 in semiurban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda, using a random age- and sex-stratified sample of the population 40 years or older.Exposures: Three screening tools, the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE; range, 0-6; high risk indicated by a score of 5 or more or score 2-5 with low PEF [<250 L/min for females and <350 L/min for males]), the COPD in LMICs Assessment questionnaire (COLA-6; range, 0-5; high risk indicated by a score of 4 or more), and the Lung Function Questionnaire (LFQ; range, 0-25; high risk indicated by a score of 18 or less) were assessed against a reference standard diagnosis of COPD using quality-assured postbronchodilator spirometry. CAPTURE and COLA-6 include a measure of PEF.Main Outcomes and Measures: The primary outcome was discriminative accuracy of the tools in identifying COPD as measured by area under receiver operating characteristic curves (AUCs) with 95% CIs. Secondary outcomes included sensitivity, specificity, positive predictive value, and negative predictive value.Results: Among 10 709 adults who consented to participate in the study (mean age, 56.3 years (SD, 11.7); 50% female), 35% had ever smoked, and 30% were currently exposed to biomass smoke. The unweighted prevalence of COPD at the 3 sites was 18.2% (642/3534 participants) in Nepal, 2.7% (97/3550) in Peru, and 7.4% (264/3580) in Uganda. Among 1000 COPD cases, 49.3% had clinically important disease (Global Initiative for Chronic Obstructive Lung Disease classification B-D), 16.4% had severe or very severe airflow obstruction (forced expiratory volume in 1 second <50% predicted), and 95.3% of cases were previously undiagnosed. The AUC for the screening instruments ranged from 0.717 (95% CI, 0.677-0.774) for LFQ in Peru to 0.791 (95% CI, 0.770-0.809) for COLA-6 in Nepal. The sensitivity ranged from 34.8% (95% CI, 25.3%-45.2%) for COLA-6 in Nepal to 64.2% (95% CI, 60.3%-67.9%) for CAPTURE in Nepal. The mean time to administer the instruments was 7.6 minutes (SD 1.11), and data completeness was 99.5%.Conclusions and Relevance: This study demonstrated that screening instruments for COPD were feasible to administer in 3 low- and middle-income settings. Further research is needed to assess instrument performance in other low- and middle-income settings and to determine whether implementation is associated with improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: There is a dearth of studies assessing non-communicable disease (NCD) mortality within population-based settings in Uganda. We assessed mortality due to major NCDs among persons ≥ 30 years in Eastern Uganda from 2010 to 2016. Methods: The study was carried out at the Iganga-Mayuge health and demographic surveillance site in the Iganga and Mayuge districts of Eastern Uganda. Information on cause of death was obtained through verbal autopsies using a structured questionnaire to conduct face-face interviews with carers or close relatives of the deceased. Physicians assigned likely cause of death using ICD-10 codes. Age-adjusted mortality rates were calculated using direct method, with the average population across the seven years of the study (2010 to 2016) as the standard. Age categories of 30–40, 41–50, 51–60, 61–70, and ≥ 71 years were used for standardization. Results: A total of 1,210 deaths among persons ≥ 30 years old were reported from 2010 to 2016 (50.7% among women). Approximately 53% of all deaths were due to non-communicable diseases, 31.8% due to communicable diseases, 8.2% due to injuries, and 7% due to maternal-related deaths or undetermined causes. Cardiovascular diseases accounted for the largest proportion of NCD deaths in each year, and women had substantially higher cardiovascular disease mortality rates compared to men. Conversely, women had lower diabetes mortality rates than men for five of the seven years examined. Conclusions: Non-communicable diseases are major causes of death among adults in Iganga and Mayuge; and cardiovascular diseases and diabetes are leading causes of NCD deaths. Efforts are needed to tackle NCD risk factors and provide NCD care to reduce associated burden and premature mortality. [ABSTRACT FROM AUTHOR]

Background: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting.Methods: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV1/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D.Trial Registration: ClinicalTrials.gov  NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD). [ABSTRACT FROM AUTHOR]

Background: Data is lacking on outcomes among COPD patients in sub-Saharan Africa. The objective of the study was to assess the incidence and predictors of mortality among COPD patients enrolled in the Uganda Registry for Asthma and COPD. Research question: What is the Incidence and predictors of mortality among COPD patients in Uganda? Study design and methods: Individuals with a diagnosis of COPD at six hospitals in Uganda were enrolled into the registry, and followed every six months. Mortality was ascertained through post-mortem reports and verbal autopsies. Mortality rates (MR), mortality rate ratios (MRR), and hazard ratios (HR) were computed to assess associations between socio-demographic, behavioural, and clinical characteristics at enrolment into the registry and mortality up to two years after. Results: We enrolled 296 COPD patients. Median age was 60 years, and 51·3% were male. The overall mortality rate was 95·90 deaths/1000 person-years. COPD severity by post-bronchodilator FEV1 was the strongest risk factor for mortality. Compared to stage 1, adjusted hazard ratios were as follows for stage 4: 9·86 (95%CI: 1·70–57·14, p = 0·011), stage 3: 6·16 (95%CI: 1·25–30·32, p = 0·025), and stage 2: 1·76 (95%CI: 0·33–9·48, p = 0·51). Underweight patients had a higher incidence of mortality compared to normal weight patients (MRR: 3·47 (95%CI: 1·45–8·31, p = 0·0026). Conclusion: Among COPD patients in Uganda, two-year mortality is high, and disease severity at baseline was the strongest risk factor for mortality. Our findings suggest the need for early, accurate, diagnosis and management of COPD, to potentially improve survival. [ABSTRACT FROM AUTHOR]

In Sub-Saharan Africa, COPD remains prevalent but its association with HIV is not well characterized especially in rural settings. We assessed for COPD prevalence, associated factors and lung function profile among HIV-infected individuals attending ART clinics in rural Nakaseke district of Uganda. We enrolled HIV-positive participants from four HIV treatment centers in rural Uganda. Participants underwent spirometry testing following standard guidelines. We defined COPD as a post-bronchodilator FEV1/FVC ratio less than the fifth percentile of the NHANES III African-American reference. We assessed for factors associated with COPD and lung function profiles using multivariable logistic and linear regression analyses. We analyzed data from 722 HIV-positive participants (mean age 48.0 years, 59.7% women). Over 90% of participants were on ART for a median duration of 4 years (IQR 2–7 years), with a median viral load of 0 copies/mL (IQR 0–0 copies/mL), current and baseline CD4 + T cell count of 478 cells/mm3 (IQR 346–663 cells/mm3) and 335 cells/mm3 (IQR 187–523 cells/mm3) respectively. The prevalence of COPD was 6.22%. COPD was associated with worse respiratory symptoms and health status. History of pulmonary tuberculosis was strongly associated with COPD (adjusted OR = 4.92, 95% CI 1.71 to 14.15, p = 0.003) and reduced lung function. Use of ART, CD4+T cell count and viral load were not associated with COPD or reduced lung function. In conclusion, we report a COPD prevalence of 6.22% in HIV-infected individuals in rural Uganda. Pulmonary tuberculosis remains the strongest predictor of COPD risk and reduced lung function in well-controlled HIV. [ABSTRACT FROM AUTHOR]

Background: More than 90% of the morbidity and mortality from chronic respiratory disease occurs in low-income and middle-income countries (LMICs), with substantial economic impact. Preserved ratio impaired spirometry (PRISm) is a prevalent lung function abnormality associated with increased mortality in high-income countries. We aimed to conduct a post-hoc analysis of a cross-sectional study to assess the prevalence of, the risk factors for, and the impact of PRISm in three diverse LMIC settings., Methods: We recruited a random, age-stratified and sex-stratified sample of the population in semi-urban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda. Quality-assured post-bronchodilator spirometry was performed to American Thoracic Society standards and PRISm was defined as a forced expiratory volume in one second (FEV 1 ) of less than 80% predicted with a FEV 1 /forced vital capacity ratio of 0·70 or more. We used t tests and χ 2 analyses to assess the relationships between demographic, biometric, and comorbidity variables with PRISm. Multivariable logistic models with random intercept by site were used to estimate odds ratios (ORs) with 95% CIs., Findings: 10 664 participants were included in the analysis, with a mean (SD) age of 56·3 (11·7) years and an equal distribution by sex. The prevalence of PRISm was 2·5% in Peru, 9·1% in Nepal, and 16·0% in Uganda. In multivariable analysis, younger age (OR for each decile of age 0·87, 95% CI 0·82-0·92) and being female (1·37, 1·18-1·58) were associated with increased odds of having PRISm. Biomass exposure was not consistently associated with PRISm across sites. Individuals with PRISm had impairment in respiratory-related quality of life as measured by the St George's Respiratory Questionnaire (OR by decile 1·18, 95% CI 1·10-1·25)., Interpretation: The prevalence of PRISm is heterogeneous across LMIC settings and associated with age, female sex, and biomass exposure, a common exposure in LMICs. A diagnosis of PRISm was associated with worse health status when compared with those with normal lung function. Health systems in LMICs should focus on all spirometric abnormalities as opposed to obstruction alone, given the disease burden, reduced quality of life, and size of the undiagnosed population at risk., Funding: Medical Research Council., Competing Interests: Declaration of interests TS reports grants or contracts from the Australian Lung Health Initiative; consulting fees from Verona Pharmaceuticals; and a leadership or fiduciary role in board, society, committee, or advocacy groups for 4D Medical. OF-F reports a Global Emerging Leader Award grant from the Fogarty International Centre. JJM reports grant support and payments made to their institution from the Alliance for Health Policy and Systems Research, Bloomberg Philanthropies, FONDECYT via CIENCIACTIVA and CONCYTEC, the British Council, British Embassy, the Newton-Paulet Fund, the UK Department for International Development, the UK Medical Research Council, the Wellcome Global Health Trials partnership, the Fogarty International Center, Grand Challenges Canada, the International Development Research Center Canada, Inter-American Institute for Global Change Research, the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Mental Health, the Swiss National Science Foundation, the UK Research and Innovation (UKRI) Biotechnology and Biological Sciences Research Council, the UKRI Engineering and Physical Sciences Research Council, the UKRI Medical Research Council, the Wellcome Trust, and the World Diabetes Foundation; a contract from Health Action International; consulting fees from the Pan American Health Organization and Bloomberg Philanthropies; participation on data safety monitoring or advisory boards for the Nigeria Sodium Study, the Intensive care bundle with blood pressure Reduction in Acute Cerebral haemorrhage Trial, the Latin American Brain Health institute, Universidad Adolfo Ibáñez (Chile), Programa de Gastronomía, Facultad de Estudios Interdisciplinarios, Pontificia Universidad Católica del Perú, and the InterAmerican Heart Foundation; being Co-chair of the Independent Group of Scientists, 2023 Global Sustainable Development Report, UN; being a member of the Scientific Expert Committee, Global Data Collaborative for CV Population Health, the World Health Federation, Microsoft, and Novartis Foundation; being a member of the Scientific and Technical Advisory Committee for the Alliance for Health Policy and Systems Research, WHO; being a member of WHO's Technical Advisory Group on non-communicable disease-related research and innovation, Non-communicable Diseases Department, WHO; and being a member of the Advisory Scientific Committee, Instituto de Investigación Nutricional, Peru. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Hypertension is diagnosed and treated based on blood pressure (BP) readings obtained in the clinic setting. Positive HIV status is associated with a higher prevalence of abnormal diurnal BP patterns, diagnosed with ambulatory BP monitoring rather than the conventional method of BP measurement. Little is known about ambulatory BP profiles in people living with HIV (PLHIV) in low-income countries, especially within sub-Saharan Africa. In this study, we compared 24-h ambulatory BP profiles of 140 HIV-positive individuals vs. profiles in 166 HIV negative individuals living in rural Uganda. HIV was well-controlled, with all HIV seropositive participants reporting use of anti-retroviral therapy, and ~123 (88%) having undetectable viral load. Most participants reported ART use duration of less than 10 years. Compared to HIV negative participants, HIV positive participants had lower median 24-h systolic BP (110.4 mmHg (IQR: 105.7, 118.7) vs 117.7 mmHg (IQR: 110.8, 129.8), p < 0.001), and 24-h diastolic BP (69.2 mmHg (IQR: 65.0, 74.9) vs. 71.9 mmHg (IQR: 67.2, 78.1), p = 0.004). Adjusted results showed greater percentage systolic nocturnal dipping among PLHIV compared to HIV negative individuals (difference = 2.70 (IQR: 0.94, 4.47), p < 0.05). Results of the adjusted Poisson regression suggested lower prevalence of 24-h and night hypertension among HIV positives compared to HIV negative, but were not statistically significant. Our data suggest that continuous 24-h BP measurements are lower in PLHIV on ART compared to HIV negative individuals., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Introduction: The association between HIV status and hypertension is not well described within sub-Saharan Africa. We examined prevalence and risk factors for hypertension among HIV positive and negative individuals living in a rural district of Uganda., Methods: We conducted a cross-sectional analysis in two concurrent cohorts of 600 HIV negative and 721 HIV seropositive individuals aged ≥35 years., Results: Of the 721 HIV positive participants, 59.8% were women and the median age was 44.3 years, while for HIV negative individuals, 55% were women and the median age was 47.8 years. Over 90% of HIV positive individuals were on antiretroviral treatment. The prevalence of hypertension (≥140/≥90 mmHg) was 33.5% in HIV negative individuals and 23.9% in HIV positive individuals. Age (adjusted OR = 1.05, 95% CI 1.03 to 1.06) and BMI (adjusted OR = 1.08, 95% CI 1.05 to 1.12) were associated with higher odds of hypertension. Having HIV was associated with lower odds of hypertension (adjusted OR = 0.66, 95% CI 0.50 to 0.88), lower systolic blood pressure (-5.1 mmHg, 95% CI: -7.4 to -2.4) and lower diastolic blood pressure (-4.0 mmHg, 95% CI: -5.6 to -2.5). We did not observe differences in the odds of hypertension by CD4 count, viral load or ART among HIV positive individuals in this sample., Conclusions: Hypertension was prevalent in one third of HIV negative individuals and in one fourth of HIV positive patients. While access to health information among individuals attending HIV clinics may explain observed differences, more research is needed to understand plausible biological and social mechanisms that could explain lower blood pressure among people living with HIV in Uganda., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Background: Low- and middle-income countries (LMICs) account for >90% of deaths and illness episodes related to COPD; however, this condition is commonly underdiagnosed in these settings. Case-finding instruments for COPD may improve diagnosis and identify individuals that need treatment, but few have been validated in resource-limited settings., Methods: We conducted a population-based cross-sectional study in Uganda to assess the diagnostic accuracy of a respiratory symptom, exposure and functional questionnaire in combination with peak expiratory flow for COPD diagnosis using post-bronchodilator FEV 1 /FVC z-score below the 5th percentile as the gold standard. We included locally relevant exposure questions and statistical learning techniques to identify the most important risk factors for COPD. We used 80% of the data to develop the case-finding instrument and validated it in the remaining 20%. We evaluated for calibration and discrimination using standard approaches. The final score, COLA (COPD in LMICs Assessment), included seven questions, age and pre-bronchodilator peak expiratory flow., Results: We analyzed data from 1,173 participants (average age 47 years, 46.9% male, 4.5% with COPD) with acceptable and reproducible spirometry. The seven questions yielded a cross-validated area-under-the-curve [AUC] of 0.68 (95% CI 0.61-0.75) with higher scores conferring greater odds of COPD. The inclusion of peak expiratory flow and age improved prediction in a validation sample (AUC=0.83, 95% CI 0.78-0.88) with a positive predictive value of 50% and a negative predictive value of 96%. The final instrument (COLA) included seven questions, age and pre-bronchodilator peak expiratory flow., Conclusion: COLA predicted COPD in urban and rural settings in Uganda has high calibration and discrimination, and could serve as a simple, low-cost screening tool in resource-limited settings., Competing Interests: Dr Robert A Wise reports personal fees from GSK, Novartis, AstraZeneca, Merck, Anapsysbio, Kikiksa, Kinevant, Galderma, Chimerx, and AbbVie, outside the submitted work. Professor John R Hursts report grants, personal fees, non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, and Novartis  that make medicines to treat COPD, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Siddharthan et al.)